Tepmetko (tepotinib) / EMD Serono - LARVOL DELTA

A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2) (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Oct 2025 ➔ May 2026

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Haematological toxicities with targeted drugs in tumors: A systematic review and network meta-analysis of randomized controlled trials (ASH 2025) - "1 patient treated with sorafenib plus chemotherapy was reported to have died as a result of pancytopenia and 1 patient treated with chemotherapy (gemcitabine plus cisplatin) died due to anemia. Our study confirmed that chemotherapy with or without a placebo, one targeted drug with chemotherapy was associated with more severe hematologic toxicities compared with the use of one targeted drug, tepotinib plus gefitinib, tivantinib plus erlotinib. In the targeted drug monotherapy category, for the primary outcome, we found that alectinib and gefitinib had a higher risk of all-grade (grade 1-5) and severe-grade (grade 3-5) anemia, respectively...Ganitumab plus chemotherapy had the highest risk of grade 1-5 anemia and thrombocytopenia. Afatinib plus chemotherapy had the highest risk of grade 3-5 anemia and thrombocytopenia. Ramucirumab plus chemotherapy had the highest risk of grade 1-5 and 3-5 neutropenia. Veliparib plus chemotherapy had the highest risk of grade 1-5 and 3-5..."

Retrospective data • Review • Febrile Neutropenia • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia

De novo and acquired MET amplification in patients (pts) with non-small cell lung cancer (NSCLC) treated with tepotinib: Results from a real-world data analysis in Australia (ESMO Asia 2025) - "In INSIGHT 2 (DCO: Mar 28, 2023), 98 pts with EGFR-mutant lung cancer and acquired METamp (in tissue by fluorescence in situ hybridization [FISH]) were treated with osimertinib and tepotinib; ORR was 50.0% (95% CI 39.7–60.3) and mPFS was 5.6 mths (95% CI 4.2–8.1). Analysis of pts in the Australian cost-share program showed that tepotinib is an effective and tolerable tx in MET-amplified NSCLC."

Clinical • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • MET • RET • TP53

Real-world efficacy and safety of tepotinib in non-small cell lung cancer patients harboring MET exon 14 skipping mutations: A retrospective, multicenter study in taiwan (MomEnTum) (ESMO Asia 2025) - "In this real-world Taiwanese cohort, tepotinib demonstrated encouraging antitumor activity and a manageable safety profile in NSCLC patients harboring MET exon 14 skipping mutations. Survival outcomes appeared more favorable when tepotinib was administered as first therapy. Case collection is ongoing to further confirm treatment outcomes by clinical characteristics."

IO biomarker • Real-world • Real-world effectiveness • Real-world evidence • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET • PD-L1

MET testing and treatment (tx) sequencing after progression of disease (PD) on first-line (1L) osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and acquired MET overexpression and/or amplification (OverExp/Amp): Final analysis of a global real-world (rw) study (ESMO Asia 2025) - P2 | "Background: In the phase II SAVANNAH study (NCT03778229), osi 80 mg QD + savolitinib 300 mg BID demonstrated clinically meaningful and durable responses in EGFRm advanced NSCLC with MET OverExp/Amp after PD on 1L osi...MET-TKIs (tepotinib 52%, capmatinib 31%) and EGFR-TKIs (osi 91%) were the most common 2L txs (29% and 24%), followed by chemotherapy (CT 20%; most frequently platinum doublet 73%)... In this rw analysis, most pts had acquired MET Amp detected with NGS and limited detection of OverExp/Amp with IHC/FISH, likely indicating underutilisation of these assays. MET-TKIs and 3rd-gen EGFR-TKIs were most commonly used following PD on 1L osi and in pts with high MET cutoffs."

Clinical • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Long-term outcomes in Asian patients with MET exon 14 skipping NSCLC receiving tepotinib in the VISION study: ≥3-year follow-up data (ESMO Asia 2025) - P2 | "Long-term outcomes after ≥3-years follow-up in Asian pts were consistent with those in all pts from VISION, regardless of baseline characteristics, including pts with baseline brain metastases."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Real world outcomes with Tepotinib in a series of Indian patients with MET exon 14 skipping positive non-small cell lung cancer. (PubMed, Ecancermedicalscience) - "Utilising a robust next-generation sequencing platform, we have identified this mutation in 5.3% of cases in our cohort. In the absence of information on MET exon 14 skipping from India, this case series will throw some light on this variation in our subcontinent and highlights the fact that the real-world effectiveness of MET inhibitors like Tepotinib and Capmantinib might be lower than expected."

Journal • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Case of MET Exon 14 Skipping Mutations in Non-Small Cell Lung Cancer with Papillary Thyroid Carcinoma (APSR 2025) - "It was found across histologies, but most commonly in sarcomatoid histology. MET TKIs, tepotinib and capmatinib, appear to result in better clinical outcomes (ORR, median PFS, and OS) than regimens with no targeted therapies."

Clinical • IO biomarker • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Palliative care • Pneumonia • Pulmonary Disease • Respiratory Diseases • Sarcoma • Septic Shock • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • MET • PD-L1 • TG

COMET: Tepotinib vs Standard Treatment in Patients With Advanced MET Exon 14 Mutated Non-Small Cell Lung Cancer Previously Treated (clinicaltrials.gov) - P3 | N=133 | Recruiting | Sponsor: Intergroupe Francophone de Cancerologie Thoracique | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2025 ➔ Nov 2025

Enrollment open • Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Case Report: Severe palmoplantar hyperkeratosis and pain four months post-tepotinib initiation: A hand-foot skin reaction. (PubMed, JAAD Case Rep) - No abstract available

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor

The Impact of Clinical Evidence on the Inclusion of Non-Small Cell Lung Cancer Drugs in Brazil's Supplementary Healthcare System (ISPOR-EU 2025) - "Favorable recommendations were issued for brigatinib, lorlatinib as first-line treatment, and osimertinib, all supported by Phase 3 trials, with network meta-analyses for brigatinib and lorlatinib. Unfavorable decisions were observed for lorlatinib as a second-line treatment, tepotinib, and selpercatinib, which relied primarily on Phase 2 data, although selpercatinib also included some Phase 3 evidence... Regulatory decisions by ANS are influenced by the robustness of clinical trial evidence. These findings suggest that submissions relying solely on early-phase studies may face greater barriers to approval. This analysis provides valuable insights for optimizing future drug submission strategies within Brazil's supplementary healthcare system."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Tepotinib-Induced Cholangitis in a Patient With Non-Small Cell Lung Cancer: A Case Report. (PubMed, Respirol Case Rep) - "The liver enzyme levels decreased after drug discontinuation. This case highlights the need for careful monitoring of hepatobiliary function when prescribing MET inhibitors, particularly in patients with underlying liver disease."

Journal • Hepatology • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Primary Biliary Cholangitis • Solid Tumor

Treatment sequencing of tepotinib in patients with MET exon 14 (METex14) skipping non-small lung cancer (NSCLC): Outcomes from ≥3 years follow-up of the VISION study (COSA 2025) - "In VISION, outcomes with tepotinib across treatment lines in patients with ≥3 years follow-up demonstrated robust and durable efficacy (consistent with previously reported findings), particularly in the 1L-setting, supporting its early use in the treatment sequence."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Long-term outcomes with tepotinib for clinically relevant subgroups of patients with MET exon 14 (METex14) skipping NSCLC in the VISION study: A ≥3-year follow-up (COSA 2025) - "Tepotinib continued to show robust and durable efficacy in patients with ≥3 years follow-up, irrespective of T+/L+ status, age, smoking status, or brain metastases at baseline, consistent with previously reported findings of overall population."

Clinical • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Safety and patient-reported outcomes with tepotinib in patients with METex14 skipping NSCLC: ≥3-year follow-up of VISION (COSA 2025) - "Tepotinib demonstrated a continued manageable safety profile with no new safety signals, as well as stability in HRQoL PROs, consistent with earlier findings. These considerations support maximizing clinical benefits for this elderly patient population while maintaining their quality of life."

Clinical • Patient reported outcomes • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC) from the VISION study: ≥3-year follow-up outcomes (COSA 2025) - P2 | "Tepotinib continued to demonstrate robust and durable activity across treatment lines. Importantly, outcomes in patients with METex14 skipping were consistent with previous results, reinforcing tepotinib as a meaningful treatment option in this setting."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Small molecule MET kinase inhibitors: Evolution, rational design, and early clinical knowledge. (PubMed, Life Sci) - "The story of the development of these inhibitors is traced here from initial, non-selective lead molecules such as K252a to the clinically approved drugs like Capmatinib and Tepotinib. A critical analysis of the failures of previous clinical trials underscores the crucial role of robust, biomarker-driven patient selection and the use of physiologically relevant preclinical models. Finally, the successful development of contemporary MET inhibitors for cancers with specific alterations, such as MET exon 14 skipping, serves as a paradigm of iterative oncology learning, wherein early failures have given rise to precision medicine and enhanced therapeutic outcomes."

Journal • Review • Oncology

A Concise Review of the Approved MET TKIs (Savolitinib, Gumarontinib, Vebreltinib, Tepotinib, Capmatinib) in China for MET Exon 14 Splice Site Mutated (METex14+) NSCLC Circa 2025. (PubMed, Lung Cancer (Auckl)) - P3 | "Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Brief Report: MET driven resistance to sotorasib in KRAS G12C-mutant Non-small cell lung cancer and response to combined KRAS and MET inhibition (JTO Clinical and Research Reports) - "Nine patients with paired pre- and post-treatment biopsies were identified. High-level MET amplification was detected by FISH in four cases and intermediate-level amplification in one case after progression on sotorasib. Notably, one patient with acquired MET amplification achieved a renewed partial response to the combination of sotorasib and tepotinib after progression on sotorasib monotherapy."

Retrospective data • Non Small Cell Lung Cancer

A UNIQUE CASE OF LUNG ADENOCARCINOMA WITH CONCURRENT ALK REARRANGEMENT AND DE NOVO MET EXON 14 SKIPPING MUTATION (CHEST 2025) - "To the best of our knowledge, this is the first reported case of metastatic lung adenocarcinoma harboring both ALK and de novo METex14 mutation on presentation, treated successfully with combination ALK-Tyrosine kinase inhibitors (TKI) and MET inhibitor therapy, without any significant adverse effects. The combination of Alectinib and Tepotinib may represent an effective treatment option for ALK+ NSCLC with de novo METex14 mutation. This case also highlights the potential for de novo METex14 mutations to serve as a mechanism of intrinsic resistance to ALK-TKIs, reflecting the importance of early detection of such mutations."

Clinical • Back Pain • Lung Adenocarcinoma • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • ALK • BRAF • EGFR • EML4 • HER-2 • KRAS • MET • ROS1

Long-term outcomes with tepotinib for clinically relevant subgroups of patients (pts) with MET exon 14 (METex14) skipping NSCLC in the VISION study: A ≥3-year follow-up (ESMO 2025) - P2 | "DOR, duration of response; m, median; mo, months; ORR, objective response rate; OS, overall survival; PFS, progression-free survival. Conclusions Tepotinib continued to show robust and durable efficacy in pts with ≥3 years follow-up, irrespective of T+/L+ status, age, smoking status, or brain metastases at baseline, consistent with previously reported findings of the overall population."

Clinical • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Treatment (Tx) sequencing of tepotinib in patients (pts) with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC): Outcomes from ≥3 years follow-up of the VISION study (ESMO 2025) - P2 | "CT, chemotherapy; DOR, duration of response; IO, immunotherapy; m, median; mo, months; ORR, objective response rate; PFS, progression-free survival; pts, patients; Tx, treatment. Conclusions In VISION, outcomes with tepotinib across Tx lines in pts with ≥3 years follow-up demonstrated robust and durable efficacy (consistent with previously reported findings), particularly in the 1L-setting, supporting its early use in the Tx sequence."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Efficacy of tepotinib for brain metastases in patients with MET exon 14 skipping non-small cell lung cancer: The REAL-MET study, a multicenter retrospective analysis (ESMO 2025) - "Conclusions Tepotinib has shown good short-term efficacy in real-world patients with METex14 skipping NSCLC and brain metastases. However, a lower rate of subsequent therapy and poorer long-term outcomes have been observed in this group."

IO biomarker • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET • PD-L1

Tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC) from the VISION study: ≥3-year follow-up outcomes (AACR-NCI-EORTC 2025) - P2 | "In VISION patients with ≥3-years follow-up, tepotinib continued to demonstrate robust and durable activity across treatment lines. Importantly, outcomes in patients with METex14 skipping were consistent with previous results, reinforcing tepotinib as a meaningful treatment option in this setting."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Treatment (Tx) sequencing of tepotinib in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC): Outcomes from ≥3 years follow-up of the VISION study (AACR-NCI-EORTC 2025) - "In VISION, outcomes with tepotinib across Tx lines in patients with ≥3 years follow-up demonstrated robust and durable efficacy (consistent with previously reported findings), particularly in the 1L-setting, supporting its early use in the Tx sequence."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET